A RIKEN-led research group has uncovered a previously unreported locus or area of chromosome in which single nucleotide polymorphisms (SNPs) are highly associated with type 2 diabetes in populations of East Asian and European descent.
The finding could lead to a diagnostic test. And studies of the principal gene’s role in the development and progress of the disease could reveal useful target compounds for drugs to prevent or treat the condition.
Type 2 or adult onset diabetes affects more than 200 million people worldwide and that number is increasing. What makes people susceptible is not fully clear, but a combination of many genes and environmental factors is likely. Recent advances in the technology to find specific SNPs in an entire individual genome have made it possible to determine which SNPs or groups of SNPs are associated with particular diseases. Several studies involving type 2 diabetics in the US and Europe have already picked out at least 16 loci associated with their condition, but no one had investigated entire individual genomes of people of East Asian ancestry.
So researchers from RIKEN’s Center for Genomic Medicine in Yokohama and institutes in Japan, Denmark and Singapore compared SNPs of type 2 diabetics with those of non-diabetics in groups from those three countries. They report their findings in a letter to Nature Genetics1.
Initially the researchers conducted a genome-wide association study in Japan of more than 207,000 SNPs. Analyzing their results statistically, they selected the 8,323 SNPs most associated with the condition, and tested these further. Eventually they pared their original number of SNPs down to six from three loci. Two of those loci were known to be highly associated with type 2 diabetes from the earlier studies, but one, based around the gene KCNQ1, was new. When tested in populations of East Asian descent in Singapore and European descent in Denmark, it was highly associated with type 2 diabetes in them as well.
KCNQ1 encodes a protein involved in forming pores enabling potassium ions to move out of cells. Mutations in the gene are reported to cause significant problems in the heart, but also in the inner ear, stomach and several other organs.
“We now want to examine the role of KCNQ1 in type 2 diabetes using animal models or cell cultures,” says project leader Shiro Maeda. “And we wish to continue our studies to discover more susceptibility genes.”
1. Unoki, H., Takahashi, A., Kawaguchi, T., Hara, K., Horikoshi, M., Andersen, G., Ng, D.P.K., Holmkvist, J., Borch-Johnsen, K., Jørgensen, T., et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nature Genetics 40, 1098–1102 (2008).
The corresponding author for this highlight is based at the RIKEN Laboratory for Endocrinology and Metabolism
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